8-89953700-TAAAA-TAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002485.5(NBN):c.1398-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,578,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: NBN NM_002485.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

Genes affected

NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 8-89953700-TA-T is Benign according to our data. Variant chr8-89953700-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 530780.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5	c.1398-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265433.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8	c.1398-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002485.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 150902 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000193

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000184 AC: 263 AN: 1427734 Hom.: 0 Cov.: 30 AF XY: 0.000189 AC XY: 134 AN XY: 710342

Gnomad4 AFR exome AF: 0.000246

Gnomad4 AMR exome AF: 0.000446

Gnomad4 ASJ exome AF: 0.0000392

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000347

Gnomad4 FIN exome AF: 0.000750

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.0000848

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 150902 Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2 AN XY: 73638

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000662

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000193

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00170 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly, normal intelligence and immunodeficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587780555; hg19: chr8-90965928;